Neuronal calcium sensor-1

Neuronal calcium sensor 1
250px PDB rendering based on 1g8i.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1G8I, 2LCP, 4GUK
Identifiers
Symbols	NCS1 ; FLUP; FREQ
External IDs	OMIM: 603315 MGI: 109166 HomoloGene: 5719 GeneCards: NCS1 Gene
Gene ontology Molecular function • magnesium ion binding • voltage-gated calcium channel activity • calcium ion binding • protein binding • protein kinase binding Cellular component • cytoplasm • cytosol • plasma membrane • postsynaptic density • cell junction • axon • dendrite • dense core granule • Golgi cisterna membrane • intracellular membrane-bounded organelle • postsynaptic membrane • perinuclear region of cytoplasm • extracellular exosome Biological process • regulation of neuron projection development • positive regulation of exocytosis • phosphatidylinositol-mediated signaling • calcium ion transmembrane transport Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23413	14299
Ensembl	ENSG00000107130	ENSMUSG00000062661
UniProt	P62166	Q8BNY6
RefSeq (mRNA)	NM_001128826	NM_019681
RefSeq (protein)	NP_001122298	NP_062655
Location (UCSC)	Chr 9: 130.17 – 130.24 Mb	Chr 2: 31.25 – 31.3 Mb
PubMed search	[1]	[2]

Neuronal calcium sensor-1 (NCS-1) also known as frequenin homolog (Drosophila) (freq) is a protein that is encoded by the FREQ gene in humans. NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins.

Function

NCS-1 regulates synaptic transmission, helps control the dynamics of nerve terminal growth, is critical for some forms of learning and memory in C. elegans and mammals, regulates corticohippocampal plasticity; and enhancing levels of NCS-1 in the mouse dentate gyrus increases spontaneous exploration of safe environments,potentially linking NCS-1 to curiosity.

NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein.

Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal secretory vesicles and regulate neurosecretion.

1. It is the Ca²⁺-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase, PIK1
2. It binds to many proteins, some in calcium dependent and some in calcium independent ways, and switches many of the targets "on" (some off).
   1. Calcineurin (protein phosphatase 2B)
   2. GRK2 (G-protein-coupled receptor kinase 2)
   3. D₂ dopamine receptor
   4. IL1RAPL1 (interleukin-1 receptor accessory protein-like 1 protein)
   5. PI4KIIIβ (type III phosphatidylinositol 4-kinase β)
   6. IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment of bipolar disorder)
   7. 3',5'-cyclic nucleotide phosphodiesterases
   8. ARF1 (ADP Ribosylation factor 1)
   9. A type (K_v4.3; Shal-related subfamily, member 3) voltage-gated potassium channels
   10. Nitric oxide synthase
   11. TRPC5 channel
   12. Ric8a
3. Frq modulates Ca²⁺ entry through a functional interaction with the α₁ voltage-gated Ca²⁺-channel subunit.

Structure

NCS-1 is a globular protein consisting of ten alpha-helices. Four pairs of alpha-helices each form independent 12-amino-acid loops containing a negatively charged calcium binding domain known as an EF-hand. However, only three of these EF hands are functional in NCS-1 (the most N-terminal EF hand does not bind calcium). NCS-1 also contains at least two known protein binding domains, and a large surface exposed hydrophobic crevice containing EF-hands three and four. There is a myristoylation motif at the N-terminus that presumably allows NCS-1 to associate with lipid membranes.

Clinical significance

The expression of NCS-1 increases in bipolar disorder and some forms of schizophrenia and decreases in inflammatory bowel disease. NCS-1 has also been linked with Autism. In addition NCS-1 is significant in intelligence in creating curiosity by its function on dopamine D2 receptors in the dentate gyrus, increasing memory for complex tasks. http://www.physorg.com/news172174436.html

History

NCS-1 was originally discovered in Drosophila as a gain-of-function mutation associated with frequency-dependent increases in neurotransmission. A role in neurotransmission was later confirmed in Drosophila using frq null mutants. Work in bovine chromaffin cells demonstrated that NCS-1 is also a modulator of neurotransmission in mammals. The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the case.

External links

• Signaling_gateway
• NCS proteins